Recombinant Human Growth Hormone Inhibits Lipotoxicity, Oxidative Stress, and Apoptosis in a Mouse Model of Diabetic Cardiomyopathy.

Zuowei Pei,Chenguang Yang,Xiang Wang,Min Dong,Fang Wang,Juan Gambini

doi:10.1155/2021/3899356

Abstract

Recombinant human growth hormone (rhGH), widely used in clinical studies, exerts protective effects against cardiac damage. Here, we investigated the effects and mechanisms underlying the effects of rhGH on cardiac functions in db/db mice. C57BL/6J and db/db mice were subjected to rhGH treatment. Metabolic parameters, cardiac function and morphology, oxidative stress, lipid metabolism, and apoptosis were evaluated 16 weeks after rhGH treatment. Although rhGH did not significantly affect fasting blood glucose levels in db/db mice, it protected against diabetic cardiomyopathy, by improving cardiac function and reducing oxidative stress in the heart. In addition, rhGH treatment exhibited anti-apoptotic effects in the heart of db/db mice. The rhGH treatment, besides inhibiting oxidative stress and apoptosis, ameliorated cardiac dysfunction by inhibiting lipotoxicity in mice with type 2 diabetes. These findings suggest that rhGH is a promising therapeutic agent for diabetic cardiomyopathy.

Highlights

Unlike healthy individuals, patients with diabetes are 2-3-fold more likely to develop cardiovascular disease and have a higher risk of developing myocardial infarction, heart failure, or stroke [1, 2]
The protective effects of Recombinant human growth hormone (rhGH) in Diabetic cardiomyopathy (DCM) might depend on the regulation of lipid metabolism
To determine whether rhGH protected the heart against DCM, cardiac function and morphology were assessed

Summary

Introduction

Patients with diabetes are 2-3-fold more likely to develop cardiovascular disease and have a higher risk of developing myocardial infarction, heart failure, or stroke [1, 2]. Diabetic cardiomyopathy (DCM) is a serious diabetic cardiovascular complication, characterized by cardiac structural remodeling and dysfunction, and is related to various pathological conditions, including myocardial lipotoxicity, oxidative stress, glucose (Glu) toxicity, cellular apoptosis, autophagy, and Fundc1-dependent mitophagy [3–8]. Mitochondrial fission and mitophagy are involved in organ damage observed under diabetic condition [9]. Lipotoxicity and oxidative stress are believed to be the two main factors contributing to the pathogenesis of DCM induced by type 2 diabetes mellitus (T2DM) [11]. Effective strategies to prevent or improve cardiac damage in patients with diabetes are yet to be devised

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Results

Conclusion